Highly Enantioselective Zirconium-Catalyzed Cyclization of Aminoalkenes

TitleHighly Enantioselective Zirconium-Catalyzed Cyclization of Aminoalkenes
Publication TypeJournal Article
Year of Publication2013
AuthorsManna K, Everett WC, Schoendorff G, Ellern A, Windus TL, Sadow AD
Journal TitleJournal of the American Chemical Society
Date Published05
Type of ArticleArticle
ISBN Number0002-7863
Accession NumberWOS:000319250200026
Keywords(r)-1,1'-binaphthyl-2,2'-diamido ligands, alkene hydroamination, alkenes, asymmetric intramolecular hydroamination, ate complexes, h bond formation, hydroamination, intermolecular, kinetic resolution, sigma-insertive mechanism, substituted, unactivated, unprotected amino olefins

Aminoalkenes are catalytically cyclized in the presence of cyclopentadienylbis(oxazolinyl)borato group 4 complexes {PhB(C5H4)(Ox(R))(2)}M(NMe2)(2) (M = Ti, Zr, Hf; Ox(R) = 4,4-dimethyl-2-oxazoline, 4S-isopropyl-5,5-dimethyl-2-oxazoline, 4S-tert-butyl-2-oxazoline) at room temperature and below, affording five-, six-, and seven-membered N-heterocyclic amines with enantiomeric excesses of >90% in many cases and up to 99%. Mechanistic investigations of this highly selective system employed synthetic tests, kinetics, and stereochemistry. Secondary aminopentene cyclizations require a primary amine (1-2 equiv vs catalyst). Aminoalkenes are unchanged in the presence of a zirconium monoamido complex {PhB(C5H4)(Ox(4S-iPr,Me2))(2)}Zr(NMe2)Cl or a cyclopentadienylmono(oxazolinyl)borato zirconium diamide {Ph2B(C5H4)-(Ox(4S-iPr,Me1))}Zr(NMe2)(2). Plots of initial rate versus [substrate] show a rate dependence that evolves from first-order at low concentration to zero-order at high concentration, and this is consistent with a reversible substrate-catalyst interaction preceding an irreversible step. Primary kinetic isotope effects from substrate conversion measurements (k'((H))(obs)/k'((D))(obs) = 3.3 +/- 0.3) and from initial rate analysis (k(2)((H))/k(2)((D)) = 2.3 +/- 0.4) indicate that a N-H bond is broken in the turnover-limiting and irreversible step of the catalytic cycle. Asymmetric hydroamination/cyclization of N-deutero-aminoalkenes provides products with higher optical purities than obtained with N-proteo-aminoalkenes. Transition state theory, applied to the rate constant k(2) that characterizes the irreversible step, provides activation parameters consistent with a highly organized transition state (Delta S-double dagger = -43(7) cal.mol(-1) K-1) and a remarkably low enthalpic barrier (Delta H-double dagger = 6.7(2) kcal.mol(-1)). A six-centered, concerted transition state for C-N and C-H bond formation and N-H bond cleavage involving two amidoalkene ligands is proposed as most consistent with the current data.

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